Fruit allergy and anaphylaxis in children: Culprit fruits and clinical findings.

Background: Fruit allergy usually presents with mild-to-moderate symptoms but serious systemic reactions, e.g., anaphylaxis, may also occur. Objective: This study aimed to examine the clinical and laboratory characteristics of patients with fruit allergy and fruit-induced anaphylaxis. Methods: Patients diagnosed with fruit allergy at Diskapi Hematology and Oncology Hospital and Bilkent City Hospital between January 2017 and January 2023 were included in the study. The diagnosis of anaphylaxis was made according to the European Allergy and Clinical Immunology Anaphylaxis Guideline. Results: During the study period, skin-prick tests with food allergens were performed on 9432 patients in our clinic, and fruit allergy was detected in 78 patients (0.82%). Five patients with inaccessible medical records were excluded from the study. 40 (54.8%) were boys. The median (interquartile range) age at the onset of symptoms was 72 months (12.5-144 months). Sixty-eight of the patients (93.2%) had a concomitant allergic disease, the most common of which was allergic rhinitis (n = 48 [65.8%]). The 73 patients had a history of reaction to 126 fruits. Twenty-five patients (19.8%) were allergic to multiple fruits. The most common fruit allergen was banana (22/126 [17.4%]), followed by peach (18/126 [14.2%]) and kiwi (17/126 [13.5%]). Mucocutaneous findings were observed most frequently after fruit consumption (120/126 [95.2%]). Anaphylaxis occurred in 17 patients (23.2%) with 21 fruits.The fruits most commonly associated with anaphylaxis were banana (6/21 [28.6%]) and kiwi (6/21 [28.6%]). Conclusion: Fruit allergy generally presents with mild symptoms, e.g., oral allergy syndrome, but severe systemic symptoms, e.g., anaphylaxis, can also be observed. Kiwi and banana are the fruits that most commonly cause anaphylaxis. Although more comprehensive studies are needed to comment on the development of tolerance, especially in patients with anaphylaxis, responsible fruit avoidance is still the most important strategy.

Characteristics and management of hypersensitivity reactions with rabbit anti-thymocyte globulin in pediatric patients.

Background: Anti-thymocyte globulin (ATG) has been successfully used for decades to prevent graft versus host disease before hematopoietic stem cell transplantation (HSCT) as a part of conditioning regimen. However, sometimes hypersensitivity reactions may limit its use. Objective: To evaluate hypersensitivity reactions experienced during rabbit-ATG infusion among children and present successful desensitization protocol. Methods: The medical records of pediatric patients who were given rabbit-ATG treatment at our tertiary center hospital HSCT unit between 2019 and 2022 were reviewed retrospectively. Diagnosis of the patients, age at the time of HSCT, gender, presence of hypersensitivity reaction to rabbit-ATG, and management were evaluated. Characteristics of the reaction and presence of hypersensitivity reaction to other drugs were also noted. If performed, desensitization protocols were evaluated retrospectively. Results: We evaluated 81 patients; 66.6% of them (n = 54) were boys. The mean age of the patients was 8.78 ± 5.48 years. Hypersensitivity to rabbit-ATG was seen in six patients (7.4%). Four of them (4.9%) had anaphylaxis; two (2.4%) had urticaria. Intradermal test performed to every patient before the first dose of ATG infusion was detected a positive result in 1 patient (1.2%) . None of these seven patients had allergic reactions to other drugs before. Successful ATG desensitization was performed in five patients by using a 12-16 step protocol due to patients' reaction severity. Conclusion: This study aimed to evaluate hypersensitivity reactions with rabbit-ATG in children. A successful desensitization protocol with rabbit-ATG is presented. Desensitization must be performed with an experienced team very carefully in the absence of alternative drug.

Clinical and Demographic Characteristics of Cutaneous Mastocytosis in Childhood: Single-center Experience.

INTRODUCTION: Mastocytosis is a rare and heterogenous disease, and in children it is generally limited to the skin and tends to regress spontaneously in adolescence. AIM: In this study, demographic, clinical, and laboratory characteristics of pediatric patients with mastocytosis, and also coexisting diseases were investigated. RESULTS: A total of 61 pediatric patients were included in the study. The male-to-female ratio was 2.2, the median age was 2 years (range, 0.25 to 19 y), and the median follow-up period was 2.0 years (range, 0.25 to 19 y). Types of clinical presentation at diagnosis consisted of mainly urticaria pigmentosa (45.9%). Seven patients were further investigated with suspicion of systemic mastocytosis, they were followed up, median of 9 years (range, 2.5 to 16 y), and none of them developed systemic disease. Coexisting allergic diseases were recorded in total 5 patients (8.2%). Three patients had immunoglobulin A deficiency, 1 patient had elevated immunoglobulin E level. A patient developed mature B-cell lymphoma with a heterozygous mutation in c-KIT exon 11. DISCUSSION: Cutaneous mastocytosis in children may present as a complex disease with different clinical signs and symptoms. Standardized clinical criteria and guidelines for the follow-up of children with mastocytosis are required.

Evaluation of Hypersensitivity Reactions in Pediatric Patients Using Biological Drugs.

INTRODUCTION: Biological drugs are currently used for the treatment of chronic inflammatory, autoimmune, and neoplastic diseases. With their expanding indication spectrum and increasing use, hypersensitivity reactions to these drugs are also becoming more frequent. The present study aimed to report the incidence and the features of such reactions in pediatric patients using biologicals for the treatment of various diseases. METHODS: The medical records of pediatric patients treated with biological agents between October 1, 2011 and August 31, 2019 were reviewed and adverse reactions were evaluated retrospectively. RESULTS: During the study period, 211 patients (116 boys, 55%) used 21 different biological drugs for the treatment of various diseases. Their median age at the time of the first treatment was 139.9 (IQR: 92.2-187.8) months. Hematologic-oncologic diseases were the most common indication for biological therapy (97/211; 46.0%), followed by rheumatologic diseases (82/211; 38.9%). Of the 211 patients, 14 (6.64%) experienced reactions to biological drugs. The most common culprit agent was rituximab (57.1%). Most of the patients (85.7%) had a history of reactions either during the infusion or within 1 h after taking the drug. Five patients underwent desensitization to the culprit drug, while 7 other patients continued treatment with a reduced dose/infusion rate or premedication. Also 1 patient continued to take the drug without any additional treatment. CONCLUSION: It was reported that 6.64% of the patients who received biologic drug therapy for various reasons in our hospital had hypersensitivity. The most common culprit agent was rituximab, and most of the reactions were immediate reactions.

Genomic Spectrum and Phenotypic Heterogeneity of Human IL-21 Receptor Deficiency.

Biallelic inactivating mutations in IL21R causes a combined immunodeficiency that is often complicated by cryptosporidium infections. While eight IL-21R-deficient patients have been reported previously, the natural course, immune characteristics of disease, and response to hematopoietic stem cell transplantation (HSCT) remain to be comprehensively examined. In our study, we have collected clinical histories of 13 patients with IL-21R deficiency from eight families across seven centers worldwide, including five novel patients identified by exome or NGS panel sequencing. Eight unique mutations in IL21R were identified in these patients, including two novel mutations. Median age at disease onset was 2.5 years (0.5-7 years). The main clinical manifestations were recurrent bacterial (84.6%), fungal (46.2%), and viral (38.5%) infections; cryptosporidiosis-associated cholangitis (46.2%); and asthma (23.1%). Inflammatory skin diseases (15.3%) and recurrent anaphylaxis (7.9%) constitute novel phenotypes of this combined immunodeficiency. Most patients exhibited hypogammaglobulinemia and reduced proportions of memory B cells, circulating T follicular helper cells, MAIT cells and terminally differentiated NK cells. However, IgE levels were elevated in 50% of IL-21R-deficient patients. Overall survival following HSCT (6 patients, mean follow-up 1.8 year) was 33.3%, with pre-existing organ damage constituting a negative prognostic factor. Mortality of non-transplanted patients (n = 7) was 57.1%. Our detailed analysis of the largest cohort of IL-21R-deficient patients to date provides in-depth clinical, immunological and immunophenotypic features of these patients, thereby establishing critical non-redundant functions of IL-21/IL-21R signaling in lymphocyte differentiation, humoral immunity and host defense against infection, and mechanisms of disease pathogenesis due to IL-21R deficiency. Outcome following HSCT depends on prior chronic infections and organ damage, which should thus be considered as early as possible following molecular diagnosis.

Can serum periostin, YKL-40, and osteopontin levels in pre-school children with recurrent wheezing predict later development of asthma?

BACKGROUND: Currently, there are no reliable clinical tools available for predicting asthma in pre-school-aged children with recurrent wheezing. The aim of this study was to evaluate the usefulness of serum periostin, YKL-40, and osteopontin biomarkers in wheezy pre-school-aged children for predicting the development of asthma in school ages. METHODS: The study was prospectively conducted between 2011 and 2017. The clinical features of the pre-school-aged children with recurrent wheezing and the levels of serum periostin, YKL-40, and osteopontin were measured. The same participants were reevaluated in school-age period, and participants with asthma were identified. Relative risk (RR) for the development of asthma was analyzed. RESULTS: Of the 197 pre-school-aged children with recurrent wheezing who were reevaluated in school-age years, 32% of them had asthma. Serum periostin, YKL-40, and osteopontin levels at admission could not predict participants who would have asthma symptoms in school-age years. The RR for continuing of asthma symptoms was higher in participants who had their first wheezing episode before 1 year of age, preterm birth, cesarean section delivery, prenatal smoking exposure, multi-trigger wheezing, parental asthma, modified asthma predictive index positivity, prophylactic vitamin D intake ≤ 12 months, breastfeeding time ≤ 12 month, and aeroallergen sensitivity [RR (95% CI) and P value: 2.813 (1.299-6.091), 0.002; 1.972 (1.274-3.052), 0.009; 1.929 (1.195-3.114), 0.004; 2.232 (1.463-3.406), <0.001; 3.152 (1.949-5.097), <0.001; 1.730 (1.144-2.615), 0.016; 2.427 (1.559-3.777), <0.001; 2.955 (1.558-5.604), <0.001; 1.767 (1.084-2.881), 0.016; 0.765 (0.556-1.053), 0.016; respectively]. CONCLUSION: Results have shown that clinical features were more valuable than biomarkers in predicting having asthma in school-age years in participants who had recurrent wheezing in pre-school-age period.

Evaluation of hypersensitivity reactions to cancer chemotherapeutic agents in pediatric patients.

BACKGROUND: Hypersensitivity reactions (HSRs) to chemotherapeutic agents have been increasingly documented. OBJECTIVE: The aim of this study was to investigate HSRs due to chemotherapeutics agents in childhood. METHODS: From January 2007 to June 2019, the patients who were treated for neoplastic diseases in our hospital were evaluated. Patients who developed a HSR to a chemotherapeutic agent were included. RESULTS: Fifty-seven patients with 65 reactions (60% anaphylaxis) were evaluated. Escherichia coli asparaginase was responsible for 38 (58.5%) of these 65 reactions. The other agents were polyethylene glycol (PEG)-asparaginase (n = 11), etoposide (n = 7), methotrexate (n = 4), carboplatin (n = 4), and procarbazine (n = 1). Of the 38 patients who had a reaction to E coli-asparaginase, 33 patients received alternative treatment (PEG-asparaginase or Erwinia asparaginase), 3 patients continued with desensitization, and 2 patients underwent bone marrow transplantation. Five patients who had an initial reaction to PEG-asparaginase continued their treatment with Erwinia asparaginase or E coli asparaginase uneventfully. Of 7 patients who had a reaction to etoposide (4 had anaphylaxis), 3 patients continued with desensitization, and 2 patients used the drug with premedication and prolonged infusion. Two patients had anaphylaxis with methotrexate. Treatment was continued with desensitization in 1 patient and methotrexate treatment was discontinued in the other patient. Of the 4 patients with carboplatin hypersensitivity, 2 had anaphylaxis. Desensitization was performed in 2 patients. One patient had procarbazine HSR, drug was given with premedication. CONCLUSION: Among all chemotherapeutic agents reviewed in our study that caused HSRs, asparaginase was the most common culprit agent in children. Most of reactions are immediate type. Many of the patients can take their treatment by drug replacement or desensitization.

The frequency of sleep-disordered breathing in children with asthma and its effects on asthma control.

BACKGROUND: The presence of sleep-disordered breathing (SDB) in children with asthma may cause difficult to control asthma. OBJECTIVES: The aim of this study was to determine the frequency of SDB in children with asthma, to evaluate its effects on asthma control and to assess the risk factors associated with the presence of SDB. METHODS: Parents of children who Sleep Questionnaire (PSQ) and the Childhood Asthma Control Test (C-ACT). Asthma control level was assessed according to Global Initiative for Asthma (GINA). Same ear-nose-throat (ENT) specialist evaluated all patients. A 4-point tonsil grading method and adenoid-nasopharynx ratio were used to categorize tonsil and adenoid size, respectively. RESULTS: A total of 408 children (275 male, 67.4%) with a mean age of 8.1 ± 3.2 years were included. Nearly 40% of asthmatic children were not-well-controlled according to GINA and 34.6% of all patients had SDB according to PSQ. Multivariate logistic regression analysis revealed that coexistence of SDB [OR: 6.62, 95% CI (4.21-10.41); p < 0.001)] and tonsillar hypertrophy [OR: 3.47; 95% CI (1.05-11.5); p < 0.041] were independent risk factors for not-well-controlled asthma in asthmatic children after other established contributors to asthma control were adjusted. CONCLUSIONS: Our study showed that SDB is a strong risk factor for not-well-controlled asthma in asthmatic children independent of other confounders. In addition, tonsillar hypertrophy may have a role in the association between SDB and not-well-controlled asthma in childhood.

Airway inflammation and bronchial hyperreactivity in steroid naive children with intermittent and mild persistent asthma.

BACKGROUND: Intermittent and mild persistent asthma are defined according to symptom frequency and spirometry and treated differently. To our knowledge, there is no study comparing airway inflammation between intermittent and mild persistent asthmatic children. MATERIALS AND METHODS: Children aged 7-16 years, referred to our pediatric allergy clinic for recurrent respiratory complaints underwent a detailed clinical history and spirometry with reversibility. None of the subjects had been using regular anti-inflammatory treatment. After a 2-week run-in period during which asthma symptoms were recorded, exhaled NO measurement, bronchial provocation test with adenosine monophosphate and methacholine and sputum induction were performed. Data of patients with intermittent and mild persistent asthma and a control group were compared. RESULTS: Thirty intermittent, 26 mild persistent asthmatic children, and 21 control subjects were studied. Sputum was obtained from 19 of intermittent asthmatics (63.3%), 18 of mild persistent asthmatics (69.2%), and 13 of control subjects (61.9%). Eosinophil count and exhaled nitric oxide were not different between asthmatic groups. Neutrophil count of children with mild persistent asthma was higher than the intermittent asthmatic group (P = 0.003). Geometric mean of PC20 methacoline values were not different between groups (P = 0.058). Geometric mean of PC20 AMP was lower among patients with mild persistent asthma (P = 0.102). CONCLUSION: Eosinophilic airway inflammation and direct BHR may not be significantly different in intermittent asthmatic children from their peers with mild persistent disease. Neutrophilic airway inflammation and BHR to an indirect stimuli are more pronounced in the mild persistent group.

A pediatric case of anaphylaxis due to octreotide.

Octreotide is an octapeptide that mimics natural somatostatin pharmacologically. It is a potent inhibitor of growth hormone, glucagon and insulin, which is used for treatment of acromegaly, symptomatic treatment of carsinoid tumours, and vasoactive intestinal peptide secreting tumors. It is also used for chylothorax, chemotherapy induced diarrhea and, as it inhibits the exocrine production of pancreatic enzymes, for acute and chronic pancreatitis. Gallbladder stones, diarrhea, nausea, vomiting, hypoglycemia/hyperglycemia, headache, and abdominal discomfort are some of the common adverse effects of octreotide and it may rarely cause anaphylaxis. We present here a child who had chronic pancreatitis and had an anaphylactic reaction to octreotide. To our knowledge this is the first pediatric case of anaphylaxis with octreotide who was successfully desensitized.